Narcotic addiction results from an interaction of opioid molecules with specific receptors in brain. In previous work, we and other workers have shown that the primary structures where morphine acts to produce depressant effects and physical dependence are located in medial regions of the subcortical brain. This phylogenetically-ancient part of the brain regulates autonomic functions of the body. In this proposal, I postulate that the physiological action of endorphins is to inhibit error signals in homeostatis feedback loops which control autonomic functions in the medial brainstem. When there is excess exogenous narcotics or endorphins, the organism becomes indifferent to signals regulating respiration, cardiovascular function, digestion, body temperature and nociception. The characteristic depressant effects of opiates and endorphins ensue: namely, decreased breathing and oxygen consumption, hypotension and bradycardia, inhibition of the defecation reflex, hypothermia and analgesia. Tolerance and dependence develop to the excess opiate agonists by amplification of the error signals and/or reduction of the agonist-receptor effect.